Dostarlimab + Cobolimab for Cervical Cancer

Recruiting at 2 trial locations

Overseen By Meghan Shea, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Meghan Shea

Must be taking: Platinum-based chemotherapy

Must not be taking: Immunosuppressants, Herbal products

Disqualifiers: Active CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 2 years

66 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use natural herbal products or other 'folk remedies' while participating in this study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the drug Dostarlimab + Cobolimab for cervical cancer?

Dostarlimab has shown promising results in treating endometrial cancer and has been approved for use in certain cases, with a 100% remission rate reported in a trial for rectal cancer. Although not directly related to cervical cancer, these results suggest potential effectiveness in other cancers. ^{1 2 3 4 5}

Is Dostarlimab safe for humans?

Dostarlimab has been approved for use in certain types of cancer, like endometrial cancer, based on its ability to shrink tumors. While it has shown promise, its safety continues to be monitored through ongoing trials to ensure it is safe for humans. ^{1 4 5 6 7}

How is the drug Dostarlimab + Cobolimab unique for treating cervical cancer?

Dostarlimab is a novel drug that works by blocking a protein called PD-1, which helps the immune system attack cancer cells. It has shown promising results in treating other cancers like endometrial and rectal cancer, and its combination with Cobolimab for cervical cancer could offer a new approach by potentially enhancing the immune response against the tumor. ^{1 3 4 5 8}

What is the purpose of this trial?

This research is being done to determine how effective dostarlimab in combination with cobolimab is in metastatic or recurrent cervical cancer.

Research Team

Meghan Shea, MD

Principal Investigator

Beth Israel Deaconess Medical Center

Eligibility Criteria

This trial is for adults with measurable, recurrent or metastatic cervical cancer. They must have good organ function and performance status, no severe prior treatment side effects, and not be pregnant or breastfeeding. Those previously treated for hepatitis C can join if cured. Exclusions include past immune checkpoint inhibitor therapy, recent chemo or radiotherapy, active autoimmune diseases, HIV/AIDS, current serious illnesses, use of immunosuppressants or live vaccines recently.

Inclusion Criteria

My cancer can be measured by standard health scans.

My organs and bone marrow are functioning well.

I had hepatitis C but have been treated and cured.

Exclusion Criteria

I have never had any type of cancer other than my current diagnosis.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to dostarlimab or cobolimab

I have a history of lung scarring or fibrosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab and cobolimab daily in 21-day cycles for up to 2 years

Up to 2 years

Day 1 of each 21-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment with imaging tests every 3 months for 2 years, then every 6 months for an additional 5 years

7 years

Every 3 months for 2 years, then every 6 months for 5 years

Treatment Details

Interventions

• Cobolimab
• Dostarlimab

Trial Overview The study tests the effectiveness of combining two drugs: Dostarlimab and Cobolimab in treating advanced cervical cancer that has spread (metastatic) or returned after treatment (recurrent). The goal is to see how well these drugs work together against this type of cancer.

Participant Groups

Group I: Cohort B: Immunotherapy Exposed Experimental Treatment 2 Interventions

14 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day of 21 Day cycle: Predetermined dose of Dostarlimab 1x daily. Predetermined dose of Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 23 additional participants will be enrolled.

Group II: Cohort A: Immunotherapy Naive Experimental Treatment 2 Interventions

10 Participants will complete study procedures as follows: * Baseline visit. * Imaging tests at baseline visit, at week 9, and then every 12 weeks. * Cycle 1 through End of Treatment (up to 2 years of treatment): • Day 1 of 21 Day cycle: Dostarlimab 1x daily and Cobolimab 1x daily. * End of Treatment visit with blood tests and imaging tests. * Follow Up Period: Every 3 months for 2 years and then every 6 months for an additional 5 years. Includes imaging tests. If \>= 2 participants with objective responses, then 19 additional participants will be enrolled.

Who Is Running the Clinical Trial?

Meghan Shea

Lead Sponsor

Trials

1

Recruited

70+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

In a phase II trial involving 155 women with recurrent or metastatic cervical cancer, the combination of balstilimab and zalifrelimab showed a confirmed objective response rate (ORR) of 25.6%, indicating promising efficacy in this patient population.

The treatment demonstrated favorable tolerability, with the most common immune-mediated adverse events being hypothyroidism (14.2%) and hyperthyroidism (7.1%), suggesting that the combination therapy is manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. O'Malley, DM., Neffa, M., Monk, BJ., et al.[2023]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab is approved for treating advanced endometrial cancer in patients with mismatch repair deficiency, highlighting its targeted approach to a specific genetic abnormality.

Aducanumab is indicated for Alzheimer's disease and received accelerated approval based on its ability to reduce amyloid beta plaques, although its clinical efficacy remains a topic of debate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. Gettman, L.[2022]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Dual PD-1 and CTLA-4 Checkpoint Blockade Using Balstilimab and Zalifrelimab Combination as Second-Line Treatment for Advanced Cervical Cancer: An Open-Label Phase II Study. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

New Drug Update: Dostarlimab, Loncastuximab Tesirine, and Aducanumab. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. [2023]